The easiest way to complete this achievement is to earn full strength, agility, and explosives, as well as earn the Firefly and Harlington HMG-90, then go after Los Muertos. And the easiest way to do that is to complete the campaign mode entirely, then reset the gangs.
With full strength, you can take a lot of damage. With full agility, you can get away quickly, as well as get TO enemies easily and quickly. And with full explosives, you can deal out a LOT of damage with ease.
NOTE: Higher level firearms is also a plus, but not as important as the others, and driving skill is even less important. Both can help, but neither is really necessary to worry about for this.
The only case in which having more driving skill is nice would be in case you plan to earn your Roadkill King as well, or if you already have full driving skill and want to take it easy. With the Agency vehicles on 4-Star driving skill, you can easily take out a ton of gang members without breaking a sweat. Just drive around with any of them and plow through gang members as you see 'em. All three vehicles will take 'em out easy as pie (although for gang vehicles, you'll need either the Supercar or the Semi Truck for taking 'em out).